Association of mannose-binding lectin-2 gene polymorphism with the development of hepatitis C-induced hepatocellular carcinoma

Liver Int. 2011 Aug;31(7):1006-12. doi: 10.1111/j.1478-3231.2011.02522.x. Epub 2011 Apr 15.

Abstract

Background: Development of end-stage liver and graft disease is suspected to be partially determined by the individual genetic background. Mannose-binding lectin (MBL) is an important immunomodulatory factor, which is supposed to be involved in complement activation and oncogenesis. Genetic polymorphisms of MBL-2 alter MBL functionality. The aim of our study was to determine the prevalence of MBL-2 polymorphism (rs7096206) in hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) based on histological analysis of explanted livers in patients undergoing liver transplantation (LT).

Methods: One hundred and seventy-seven patients, who underwent LT for HCV-induced liver disease, were genotyped for MBL-2 by TaqMan genotyping assay. Sixty-two patients with histologically confirmed HCC were compared with 115 patients without HCC. MBL-2 genotypes were corelated with the growth patern, tumour size and pretransplant α-fetoprotein (AFP) level of HCC patients.

Results: The prevalence of GG/GC genotypes was significantly higher among HCC patients compared with tumour-free explanted livers (P = 0.004; odds ratio 2.5; 1.3-4.8). GG/GC genotype group was significantly associated with the size of HCC (P = 0.022), higher pretransplant AFP level (P = 0.010) and bilobar tumour growth (P = 0.038). Furthermore, CC genotype was found to be significantly more frequent in AFP-negative HCCs (P = 0.002).

Conclusion: Mannose-binding lectin-2 polymorphism seems to be involved in the development of pretransplant HCV-induced HCC and should be further investigated as potential risk factor for HCV-associated carcinogenesis.

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / genetics*
  • DNA Primers / genetics
  • Female
  • Genotype
  • Germany
  • Hepatitis C / complications*
  • Humans
  • Liver Neoplasms / etiology
  • Liver Neoplasms / genetics*
  • Logistic Models
  • Male
  • Mannose-Binding Lectin / genetics*
  • Middle Aged
  • Polymorphism, Genetic*
  • alpha-Fetoproteins / metabolism

Substances

  • DNA Primers
  • MBL2 protein, human
  • Mannose-Binding Lectin
  • alpha-Fetoproteins